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Biomedical subjects

J Pascual

Publications and source records attributed to J Pascual.

At least 163 records · Page 9Linked to original sources
PubMed1998

The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group.

Acute renal failure (ARF) is at a crossroads between nephrology and intensive care medicine. However, there seems to be wide differences between the ARF observed in the intensive care unit (ICU) compared to that observed in other areas of the hospital, particularly when examining the mortality rate. Among the ICU patients the 70% mortality rate is higher to the 50% found in an overall series of studies. Recently, Druml proposed that there is a changing trend in the clinical spectrum of ARF as a convincing reason to justify these differences. According to him, we are moving from an ARF seen as a mono-organ failure to another one observed in a multiorgan dysfunction syndrome (MODS) context. Although extremely coherent, this hypothesis has not been fully confirmed in a prospective study. In fact, most authors seem to look at the problem from opposite sides of the river, either from the critical medicine or the nephrological bank. To the best of our knowledge, only one retrospective study has dealt with this topic by comparing outcome of ARF in ICU and non-ICU patients. In this article we aim to overcome this problem by reviewing the data of the prospective epidemiological ARF study carried out in Madrid using two different approaches: (1) comparing the ARF cases observed in the ICU setting with those ARF studied outside the ICU, and (2) comparing the outcome of isolated ARF with the outcome of ARF as part of a MODS in patients treated in both settings.

Acute Kidney Injury↗
PubMed1998

Outcomes in acute renal failure.

Although patients with acute renal failure (ARF) are now older and sicker than in the past, mortality remains constant or even slightly lower, which suggests a better management of the syndrome. Several clinical conditions, mainly assisted respiration, hypotension, oliguria, coma and jaundice, have a detrimental effect on outcome. Previous health status, original disease, a hospital and/or ICU start of the ARF, and age of the patient also seem to affect outcome of these patients. ARF observed in the ICU setting has a poorer prognosis than the ARF treated in other hospital areas. This is because of the higher number of associated organ failures observed in the ICU. Estimation of outcome could be done either using specific ARF or general ICU score systems. They allow risk stratification of the patients, and some of them give an individual prognosis that at present should not be used for a withdrawal decision. Functional outcome of ARF is usually good, although some patients need to be maintained on chronic dialysis.

Acute Kidney Injury↗
PubMed1998

[Mechanism of action of zolmitriptan].

Zolmitriptan is a new serotonergic agonist with excellent oral bioavailability exhibiting a potent symptomatic antimigraine effect. Zolmitriptan is a selective agonist of 5-HT1B/D receptors. 5-HT1B receptors are concentrated in the wall of the cranial extracerebral arteries. 5-HT1D receptors are located on the trigeminal terminals which receive pain from the leptomeningeal vessels. Migraine pain has its origin on cranial vessels. In fact, during a migraine attack the trigeminovascular system, which is composed by the cranial vessels and its trigeminal terminals, is activated. The activation of this system induces both dilatation and aseptic inflammation of cranial vessels. Zolmitriptan blocks both vascular phenomena. Its agonist action upon the 5-HT1D receptor ends the aseptic inflammation by inhibiting the release of vasoactive peptides. The dilatation of meningeal vessels disappears due to the stimulation of zolmitriptan of 5-HT1B receptors. As this drug crosses the blood brain barrier, zolmitriptan has both peripheral and central actions over the espinal trigeminal nucleus, which is rich in 5-HT1B/D receptors. Thus, the mechanism of action of zolmitriptan is double. On the one hand, zolmitriptan acts peripherally inhibiting dilatation and inflammation of cranial vessels. On the other, zolmitriptan exhibits a central nociceptive action in the brainstem nuclei. This dual action of zolmitriptan on migraine pain is completed with its beneficial effects on nausea and vomiting, due to its binding to the nucleus of the tractus solitarius, the center for control of vomiting.

Humans↗
PubMed1997

Solution structure of the spectrin repeat: a left-handed antiparallel triple-helical coiled-coil.

Cytoskeletal proteins belonging to the spectrin family have an elongated structure composed of repetitive units. The three-dimensional solution structure of the 16th repeat from chicken brain alpha-spectrin (R16) has been determined by NMR spectroscopy and distance geometry-simulated annealing calculations. We used a total of 1035 distance restraints, which included 719 NOE-based values obtained by applying the ambiguous restraints for iterative assignment (ARIA) method. In addition, we performed a direct refinement against 1H-chemical shifts. The final ensemble of 20 structures shows an average RMSD of 1.52 A from the mean for the backbone atoms, excluding loops and N and C termini. R16 is made up of three antiparallel alpha-helices separated by two loops, and folds into a left-handed coiled-coil. The basic unit of spectrin is an antiparallel heterodimer composed of two homologous chains, beta and alpha. These assemble a tetramer via a mechanism that relies on the completion of a single repeat by association of the partial repeats located at the C terminus of the beta-chain (two helices) and at the N terminus of the alpha-chain (one helix). This tetramer is the assemblage able to cross-link actin filaments. Model building by homology of the "tetramerization" repeat from human erythrocyte spectrin illuminates the possible role of point mutations which cause hemolytic anemias.

Amino Acid Sequence↗
PubMed1997

Autoradiographic distribution of M1, M2, M3, and M4 muscarinic receptor subtypes in Alzheimer's disease.

We studied the autoradiographic densities of all pharmacologically characterised muscarinic receptors (MR) in frontal, temporal, and visual cortex, hippocampal formation, and striatum in autopsied brains from 19 histopathologically verified patients of Alzheimer's disease (AD) and in matched controls. Almost all (16 of 19) of the AD cases were severe. In AD brains, total MR, M1, and M3 MR subtypes were found to be significantly decreased in entorhinal cortex and in most hippocampal strata. Total MR and M1 receptors were also significantly reduced in visual area and in frontal cortex of AD brains, respectively. M2 receptors were significantly reduced over hippocampal formation but increased significantly in striatum of AD brains as compared with controls. M3 receptors in AD were in the range of controls in neocortex and striatum, whereas the M4 receptor subtype was also preserved in all brain regions in AD brains when compared with controls. This is the first autoradiographic study analysing the distribution of all MR subtypes in AD brains. These changes in MR densities concur with the general pattern of neuronal degeneration occurring in AD brains and partly explain the poor response of AD cognitive decline to present cholinergic supplementation therapies. Although M3 and M4 MR were labelled with nonselective approaches, the preservation of M4 and to a lesser degree M3 MR subtypes in AD brains could open an alternative way for the symptomatic therapy of AD dementia.

Aged↗
PubMed1997

Evolution of the spectrin repeat.

We now know that the evolution of multidomain proteins has frequently involved genetic duplication events. These, however, are sometimes difficult to trace because of low sequence similarity between duplicated segments. Spectrin, the major component of the membrane skeleton that provides elasticity to the cell, contains tandemly repeated sequences of 106 amino acid residues. The same repeats are also present in alpha-actinin, dystrophin and utrophin. Sequence alignments and phylogenetic trees of these domains allow us to interpret the evolutionary relationship between these proteins, concluding that spectrin evolved from alpha-actinin by an elongation process that included two duplications of a block of seven repeats. This analysis shows how a modular protein unit can be used in the evolution of large cytoskeletal structures.

Amino Acid Sequence↗
PubMed1997

125I-galanin binding sites in Alzheimer's disease: increases in hippocampal subfields and a decrease in the caudate nucleus.

Using iodinated human galanin and autoradiography, galanin binding sites were studied in cortical and hippocampal areas and in some brainstem nuclei in the brains of eight patients with senile dementia of the Alzheimer type (SDAT) and of nine matched control cases. The highest density of binding sites was found in the substantia nigra with a less intense labeling in the hippocampus and cortical regions. In the SDAT cases a significant increase in number of galanin binding sites was found in some hippocampal areas, a decrease in the caudate nucleus, and no significant changes in frontal and entorhinal cortices. These findings suggest that some central galanin systems may be deranged in SDAT.

Aged↗
PubMed1997

Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis. A report of 50 cases.

This is the first large series, comprising 50 patients who suffered a total of 164 episodes, of pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis (PMP syndrome). Onset of PMP was between the ages of 14 and 39 years and was most frequent in males (68%). Eight males (24%) and five females (31%) had a personal history of migraine. One-quarter had had a viral-like illness up to 3 weeks prior to the onset of the syndrome. The clinical picture consisted of one to 12 episodes of changing variable neurological deficits accompanied by moderate-to-severe headache and occasionally fever. The headaches were described as predominantly throbbing and bilateral with variable duration (mean, 19 h). The mean duration of the transient neurological deficits was 5 h. Sensory symptoms were most common (78% of episodes), followed by aphasic (66%) and motor (56%) symptoms. Visual symptoms appeared in only 12% of episodes. The most frequent combinations were motor aphasia plus sensory and motor right hemibody symptoms (19% of episodes), motor aphasia plus right sensory symptoms (10%) and isolated right (9%) or left (9%) sensory symptoms. All patients were asymptomatic between episodes and following the symptomatic period (maximum duration 49 days). Lymphocytic pleocytosis ranged from 10 to 760 lymphocytic cells/mm3 CSF (mean, 199). In CSF, protein was increased in 96% of patients, IgG was normal in 80% of cases and oligoclonal bands were not found. Adensoine deaminase values were slightly above normal in two out of 16 patients tested. Extensive microbiological determinations, including viral HIV and borrelia serologies, were negative. Brain CT and MRI were always within normal limits, while EEG frequently showed focal slowing. Conventional cranial angiography was performed on 12 patients. In only one were there abnormalities suggestive of localized vascular inflammation, coincident with the focal neurological symptoms. Two patients developed PMP symptoms immediately after angiography. SPECT, performed on only three patients in the symptomatic period, revealed focal areas of decreased uptake consistent with the clinical symptoms. PMP aetiology remains a mystery; chronic arachnoiditis, viral meningoencephalitis or migraine are not plausible aetiological explanations. Because a number of patients had had a prodromic viral-like illness, we hypothesize here that such a viral infection could activate the immune system, thereby producing antibodies that would induce an aseptic inflammation of the leptomeningeal vasculature, possibly accounting for this clinical picture.

Adolescent↗
PubMed1997

Cardiovascular parameters of heroin-withdrawn addicts treated with guanfacine.

Blood pressure and heart rate were monitored in heroin addicts detoxified with guanfacine in an outpatient program. Retrospective analysis of the cardiovascular parameters from the addicts who failed this detoxification during the first 5 days of treatment (they consumed heroin within this period) showed that these patients experienced less hypotension and bradycardia when treated with the alpha 2-agonist than the group of successful patients. Therefore, the relapse to opiate use could be predicted, at least in some patients, by a minimal cardiovascular reaction to guanfacine. Opiate use was followed by significant increases in blood pressure and heart rate, as had happened in previous studies with clonidine-treated addicts. This finding further confirms a similarity between alpha 2-agonists adrenergic and opiates with regard to their cardiovascular effects.

Adrenergic alpha-Agonists↗